Hallmark 12: Gut Dysbiosis

When the Gut’s Inner Ecosystem Falls Out of Balance

What Is Gut Dysbiosis?

Your gut is like a densely populated rainforest, home to trillions of microscopic residents. Together, they form what is known as the gut microbiome [1,2]. In a healthy state, this inner ecosystem is diverse and balanced. Different species perform different jobs: helping to break down food, producing vitamins, keeping the gut lining strong, and discouraging harmful invaders. Dysbiosis occurs when this balance is disturbed and helpful microbes dwindle, less helpful ones flourish, or the overall harmony of the system is lost.

How Does It Happen and Why Does It Contribute to Ageing?

Each of us develops a unique microbiome early in life. It is shaped by genetics and influenced by diet, environment, and lifestyle. For much of adulthood this internal ecosystem remains relatively stable. With age, however, gradual shifts begin to occur. Diet often becomes less varied, medications (particularly antibiotics) can disrupt microbial balance, physical activity may decline and the immune system becomes less resilient. Over time therefore,  microbial diversity tends to decrease, and communication between the microbiome and the rest of the body becomes less reliable.

Why does this matter for ageing? This matters because the gut does not function in isolation. It is in continuous dialogue with the immune system and the brain along with hormone producing tissues [3,4,5]. When the microbial ecosystem becomes imbalanced, these signals lose clarity resulting in low grade inflammation  (Remember Hallmark 11?), altered immune responses, and metabolic changes that can accelerate biological ageing [1,6].

Accumulation and Organ-Specific Effects

Certain by-products of an imbalanced microbiome have been linked to frailty and reduced physical resilience, while others appear to support strength and longevity. 

The immune system is particularly affected, an unhealthy gut can encourage a state of low-grade, persistent inflammation. This inflammatory background can make tissues more vulnerable to disease and slow recovery.

The brain, too, is influenced by the gut. Changes in the microbiome have been associated with poorer memory, reduced learning ability, and altered immune activity in the brain. In fact, In animal studies, restoring a more youthful gut environment has improved cognitive function.

Even reproductive tissues are not spared. In ageing animals, restoring a healthier microbiome improves ovarian function and reduces inflammatory damage, suggesting that gut health reaches further into the body than we once imagined.

Intriguingly, studies of centenarians, people who live beyond 100, reveal that their microbiomes often look different again. They harbour specific microbes that produce compounds thought to protect against infection and support gut stability. [2,7]

Can We Slow Down Dysbiosis to Slow Ageing?

Research into gut-based interventions is advancing rapidly. One of the most striking tools is faecal microbiota transplantation (FMT) - the transfer of gut microbes from a healthy donor to a recipient [8] (yes this is exactly what it sounds like). Although it does not sound appealing, it is already a life-saving treatment for certain severe infections. In ageing research, FMT has revealed something profound: transferring microbes from young or healthy donors to older or prematurely aged animals can improve health, reduce inflammation, and even extend lifespan. Remarkably, in some cases, introducing a single beneficial bacterial species is enough to reproduce these effects [9].

Scientists are also exploring ways to deliver the benefits of a healthy microbiome without transplants, by restoring key microbial products or encouraging the growth of protective species through targeted nutrition and medicines [10].

Another powerful intervention is caloric restriction - eating slightly less without malnutrition. This approach consistently reshapes the gut microbiome in ways associated with healthier ageing, increasing strains linked to resilience and metabolic health [11]. While human applications are still developing, the message is clear: restoring balance in the gut can influence the pace and quality of ageing across the whole body.

Lifestyle Approaches to Keep Gut Dysbiosis in Check

The encouraging news is that everyday choices really do matter when it comes to the gut, it responds quickly to how we live.

A varied, fibre-rich diet acts like diverse fuel for your microbial ecosystem, supporting a wide range of beneficial species. Regular movement encourages healthy gut activity and microbial balance. Managing stress matters too - chronic stress alters gut communication in ways that favour imbalance.

Avoiding unnecessary antibiotics, eating with regularity, and allowing time for rest and repair all help maintain microbial harmony. 

Conclusion: Why the Hallmarks of Ageing Matter

Gut dysbiosis is the final hallmark described by López-Otín and colleagues in their updated framework of ageing, and it is a fitting one. The gut connects the environment to biology, lifestyle to longevity. It reminds us that ageing is not confined to our genes or our cells, but is shaped continuously by how we live.

Since the original 2013 Hallmarks of Ageing paper, this framework has inspired hundreds of thousands of studies, transforming how scientists understand why we age and how we might age better. Other models have emerged, proposing additional hallmarks as knowledge grows, but the strength of the López-Otín framework lies in its clarity and staying power.

Together, the hallmarks provide a map that helps us understand how ageing goes wrong and, importantly, where we might intervene. By addressing these processes, not in isolation but as an interconnected system, we shift the focus from simply living longer to living better.

References: 

[1] Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Curr Opin Gastroenterol. 2015 Jan;31(1):69-75. doi: 10.1097/MOG.0000000000000139. PMID: 25394236; PMCID: PMC4290017.

[2] Wang Y, Qu Z, Chu J, Han S. Aging Gut Microbiome in Healthy and Unhealthy Aging. Aging Dis. 2024 Mar 31;16(2):980-1002. doi: 10.14336/AD.2024.0331. PMID: 38607737; PMCID: PMC11964416.

[3] Gwak MG, Chang SY. Gut-Brain Connection: Microbiome, Gut Barrier, and Environmental Sensors. Immune Netw. 2021 Jun 16;21(3):e20. doi: 10.4110/in.2021.21.e20. PMID: 34277110; PMCID: PMC8263213.

[4] Wiertsema SP, van Bergenhenegouwen J, Garssen J, Knippels LMJ. The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies. Nutrients. 2021 Mar 9;13(3):886. doi: 10.3390/nu13030886. PMID: 33803407; PMCID: PMC8001875

[5] Unlu Y, Vinales KL, Hollstein T, Chang D, Cabeza de Baca T, Walter M, Krakoff J, Piaggi P. The association between gut hormones and diet-induced metabolic flexibility in metabolically healthy adults. Obesity (Silver Spring). 2023 Jan;31(1):139-149. doi: 10.1002/oby.23584. Epub 2022 Dec 5. PMID: 36471908; PMCID: PMC9780166